Download Practical Recommendations for the Use of ACE Inhibitors

Practical recommendations for the use of
ACE inhibitors, beta-blockers and spironolactone in heart failure:
Putting Guidelines into Practice
— INTRODUCTION —
McMurray J, Cohen-Solal A, Dietz R, Eichhorn E, Erhardt L,
Hobbs R, Maggioni A, Pina I, Soler-Soler J, Swedberg K
Eur J Heart Failure 2001;3:495–502
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
•
•
•
•
•
A number of large, carefully designed clinical outcome trials have been
conducted in patients with chronic heart failure
The trials were sufficiently powered to allow unequivocal interpretation
of the results
Consequently, there now exists robust safety and efficacy information
on a number of therapeutic interventions
The translation of these results into clinical prescribing has been
slow and incomplete
Patients may therefore be denied the full benefit of proven
therapeutic interventions
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
Development of Recommendations
•
•
•
•
The speed and extent of update of evidence-based therapies (particularly ACE
inhibitors and beta-blockers) for the treatment of heart failure has been disappointing in
hospital practice and primary care
This may reflect a lack of practical advice regarding dosing issues and the
management of associated adverse events
Consequently, a group of eminent clinicians with expertise in the management of heart
failure met during 2000
The remit of the faculty was to review all the relevant published clinical trials and
produce a set of clinical recommendations independent of any other interests
Practical Recommendations for in Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
Advisory Group
John McMurray
Alain Cohen-Solal
Rainer Dietz
Eric Eichhorn
Leif Erhardt
Richard Hobbs
Aldo Maggioni
Ileana Pina
Jordi Soler-Soler
Karl Swedberg
Glasgow, UK
Clichy, France
Berlin, Germany
Dallas, USA
Malmö, Sweden
Birmingham, UK
Florence, Italy
Cleveland, USA
Barcelona, Spain
Göteborg, Sweden
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
Output
•
•
•
•
•
The output from discussions was a step-wise, concise set of clinical recommendations
concentrating on three key therapies for the management of heart failure
These recommendations are not meant to replace existing guidelines, but rather
provide a tool to facilitate their implementation
The opinions expressed are those of the faculty members and do not necessarily
reflect the views of AstraZeneca or the manufacturers of the products mentioned
Prescribers need to be aware of the relevant product prescribing information which
applies in their country
The costs associated with the Advisory Group meetings were met by an educational
grant from AstraZeneca
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
Format
The practical recommendations for treatment are reviewed under the
following headings:
 Why? – what evidence exists to support the use of these treatments
 In whom and when? – which patients, what contra-indications, what cautions and
drug interactions
 Where? – hospital or primary care setting
 Which agent and what dose? – options offered based on
outcome evidence
 How to use – titration and monitoring information
 Advice to patient – expected benefits and drawbacks
 Problem solving – management of adverse events and concomitant medications
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
Practical Recommendations
These recommendations start from the assumption that the physician has made
a clinical diagnosis of heart failure and may have initiated diuretic treatment for
treating the symptoms and signs associated with fluid overload
•
STEP 1
- Confirm left ventricular systolic dysfunction (LVSD) by echocardiography,
radionuclide ventriculography or radiological left ventricular angiography.
[These investigations are regarded as definitive and must be regarded as
representing the minimum standard of care.]
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
Practical Recommendations
•
•
STEP 2
- Initiate first-line therapy in all patients with heart failure due to LVSD with an ACE
inhibitor for NYHA class I-IV and a beta-blocker for NYHA class II-III, unless these
are contra-indicated.
- Initiate ACE inhibitor first, followed by beta-blocker, both initially at low doses and
then up-titrate slowly to the target doses used in the clinical trials, check tolerability
and blood chemistry.
STEP 3
- Initiate second-line therapy in patients with persistent signs and symptoms of heart
failure (NYHA class III/IV) with spironolactone and digoxin; contra-indications and
cautions should be observed.
- Initiate spironolactone first followed by digoxin, both at a low dose and then uptitrate, check tolerability and blood chemistry.
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— INTRODUCTION —
‘The preparation of these concise and practical clinical recommendations for the
prescribing of ACE inhibitors and beta-blockers should provide doctors with the
confidence to practise evidence-based medicine in their patients with
chronic heart failure. This would improve not only the outcomes for the individual
patient but also reduce the burden on healthcare systems.’
McMurray J, Cohen-Solal A, Dietz R, Eichhorn E, Erhardt L,
Hobbs R, Maggioni A, Pina I, Soler-Soler J, Swedberg K
Eur J Heart Failure 2001;3:495–502
Practical recommendations for the use of
ACE inhibitors, beta-blockers and spironolactone in heart failure:
Putting Guidelines into Practice
— ACE INHIBITORS —
McMurray J, Cohen-Solal A, Dietz R, Eichhorn E, Erhardt L,
Hobbs R, Maggioni A, Pina I, Soler-Soler J, Swedberg K
Eur J Heart Failure 2001;3:495–502
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
Format
The practical recommendations for treatment are reviewed under the
following headings:
 Why? – what evidence exists to support the use of these treatments
 In whom and when? – which patients, what contra-indications, what cautions and
drug interactions
 Where? – hospital or primary care setting
 Which agent and what dose? – options offered based on
outcome evidence
 How to use – titration and monitoring information
 Advice to patient – expected benefits and drawbacks
 Problem solving – management of adverse events and concomitant medications
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Why?
•
•
•
•
CONSENSUS I, the SOLVD-treatment study and a meta-analysis of smaller trials
showed conclusively that ACE inhibitors increase survival, reduce hospital admissions
and improve NYHA class and quality of life in patients with all grades of symptomatic
heart failure
ATLAS showed clinically important advantages with higher doses of ACE inhibitors in
heart failure
SAVE, AIRE and TRACE showed that ACE inhibitors increase survival in patients with
systolic dysfunction after acute myocardial infarction
SOLVD-prevention study showed that ACE inhibitors delay or prevent the development
of symptomatic heart failure in patients with asymptomatic LVSD
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
Co-operative North Scandinavian Enalapril Survival Study I – CONSENSUS I
80
70
Placebo
60
Enalapril
50
Mortality
(%)
40
30
20
Risk reduction 40%
p=0.002
10
0
1
2
3
4
5
6
7
8
9
10
11
12
Follow-up (months)
CONSENSUS Trial Study Group N Engl J Med 1987;316:1429–1435
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
Studies of Left Ventricular Dysfunction – SOLVD (Treatment Study)
50
40
Mortality
(%)
30
Placebo
Enalapril
20
10
Risk reduction 16%
p=0.0036
0
0
6
12
18
24
30
36
42
48
Follow-up (months)
SOLVD Investigators N Engl J Med 1991;325:293–302
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
Assessment of Treatment with Lisinopril and Survival Study ATLAS
100
*Combined all-cause mortality plus
all-cause hospitalisations
75
Eventfree*
survival
%
Risk reduction 12%
p=0.002
50
High-dose
25
Low-dose
0
0
6
12
18
24
30
36
Follow-up (months)
42
48
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – In Whom and When?
Indications:
• Potentially all patients with heart failure
• First-line treatment (along with beta-blockers) in NYHA class I–IV heart failure
Contra-indications:
• History of angioneurotic oedema
Cautions/seek specialist advice:
• Significant renal dysfunction (creatinine >2.5 mg/dL or 221 µmol/L) or
hyperkalaemia (K+ >5.0 mmol/L)
• Symptomatic or severe asymptomatic hypotension (SBP <90 mmHg)
Drug interactions to look out for:
• K+ supplements/ K+ sparing diuretics (including spironolactone)
• NSAIDs*
• AT1-receptor blockers
*avoid unless essential
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Where?

In the community for most patients

Exceptions – see CAUTIONS/SPECIALIST ADVICE
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Which and What Dose?
•
•
•
•
•
captopril
enalapril
lisinopril
ramipril
trandolapril
Starting dose
6.25 mg tds
2.5 mg bd
2.5–5 mg od
2.5 mg od
1 mg od
Target dose
50–100 mg tds
10–20 mg bd
30–35 mg od
5 mg bd/10 mg od
4 mg od
od = once daily; bd = twice daily; tds = thrice daily
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – How to Use
•
•
•
•
•
Start with a low dose
Double dose at not less than two weekly intervals
Aim for target dose or, failing that, the highest tolerated dose
Remember some ACE inhibitor is better than no ACE inhibitor
Monitor blood chemistry (urea, creatinine, K+) and blood pressure
•
When to stop up-titration/down-titration – see PROBLEM SOLVING
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Advice to Patient
•
•
•
•
Explain expected benefits (see WHY?)
Treatment is given to improve symptoms, to prevent worsening of heart failure
and to increase survival
Symptoms improve within a few weeks to a few months
Advise patients to report principal adverse effects
(i.e. dizziness/symptomatic hypotension, cough)
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Problem Solving
Asymptomatic low blood pressure:
• Does not usually require any change in therapy
Symptomatic hypotension:
• If dizziness, light-headedness and/or confusion and low blood pressure occur,
reconsider need for nitrates, calcium channel blockers* and other vasodilators
• If no signs/symptoms of congestion, consider reducing diuretic dose
• If these measures do not solve the problem, seek specialist advice
*calcium channel blockers should be discontinued unless absolutely essential
(e.g. for angina or hypertension)
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Problem Solving (continued)
Cough:
• Cough is common in patients with heart failure, many of whom have smoking-related
lung disease
• Cough is also a symptom of pulmonary oedema, which should be excluded if a new
or worsening cough develops
• ACE inhibitor-induced cough rarely requires treatment discontinuation
• If a very troublesome cough develops (e.g. one stopping the patient sleeping) and can
be proven to be due to ACE inhibition (i.e. it recurs after ACE inhibitor withdrawal and
rechallenge), substitution with an AT1-receptor blocker can be considered
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Problem Solving (continued)
Worsening renal function:
• Some increase in urea (blood urea nitrogen), creatinine and K+ is to be expected after
initiation; if the increase is small and asymptomatic no action is necessary
• An increase in creatinine of up to 50% above baseline, or 3 mg/dL (266 µmol/L),
whichever is the smaller, is acceptable
• An increase in K+  6.0 mmol/L is acceptable
• If urea, creatinine or K+ rise excessively, consider stopping concomitant nephrotoxic
drugs (e.g. NSAIDs), other K+ supplements/ K+ retaining agents (triamterene,
amiloride) and, if no signs of congestion, reducing the dose of diuretic
• If greater rises in creatinine or K+ than those outlined above persist, despite adjustment
of concomitant medications, halve the dose of ACE inhibitor and recheck blood
chemistry; if there is still an unsatisfactory response, specialist advice should be sought
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— ACE INHIBITORS —
ACE Inhibitors – Problem Solving (continued)
Worsening renal function (cont.):
• If K+ rises to >6.0 mmol/L, or creatinine increases by >100% or to above 4 mg/dL (354
µmol/L), the dose of ACE inhibitor should be stopped and specialist advice sought
• Blood chemistry should be monitored serially until K+ and creatinine have plateaued
NOTE: it is very rarely necessary to stop an ACE inhibitor and clinical deterioration is likely
if treatment is withdrawn; ideally, specialist advice should be sought before treatment
discontinuation
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— AT1-RECEPTOR BLOCKERS —
AT1-Receptor Blockers
•
•
•
At present, position is unclear due to inconclusive evidence from clinical trials
(ELITE I, ELITE II, Val-HeFT)
Currently, prescribing AT1-receptor blockers in heart failure should be confined
patients who are unable to tolerate ACE inhibitors
Results from the ongoing CHARM study programme, involving candesartan,
should provide a clearer picture of their role in heart failure management
to
Practical recommendations for the use of
ACE inhibitors, beta-blockers and spironolactone in heart failure:
Putting Guidelines into Practice
— BETA BLOCKERS —
McMurray J, Cohen-Solal A, Dietz R, Eichhorn E, Erhardt L,
Hobbs R, Maggioni A, Pina I, Soler-Soler J, Swedberg K
Eur J Heart Failure 2001;3:495–502
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Format
The practical recommendations for treatment are reviewed under the
following headings:
 Why? – what evidence exists to support the use of these treatments
 In whom and when? – which patients, what contra-indications, what cautions and
drug interactions
 Where? – hospital or primary care setting
 Which agent and what dose? – options offered based on
outcome evidence
 How to use – titration and monitoring information
 Advice to patient – expected benefits and drawbacks
 Problem solving – management of adverse events and concomitant medications
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Why?

•
USCP, CIBIS II, MERIT-HF and COPERNICUS have shown conclusively that
betablockers increase survival, reduce hospital admissions and improve NYHA class and
quality of life when added to standard therapy (diuretics, digoxin and
ACE
inhibitors) in patients with stable mild and moderate heart failure and in
some
patients with severe heart failure
One trial (BEST) did not show a reduction in all-cause mortality but did report a
reduction in cardiovascular mortality
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
United States Carvedilol Program (USCP)
Survival
(%)
100
95
90
85
80
75
70
65
60
55
Carvedilol
Placebo
Risk reduction 65%
p=0.0001
0
50
100
150
200
250
300
350
400
Duration of therapy (days)
Packer M et al. N Engl J Med 1996;334:1349–1355
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Cardiac Insufficiency Bisoprolol Study II (CIBIS II)
100
Survival
(%)
Bisoprolol
80
Placebo
60
Risk reduction 34%
p<0.0001
0
0
200
400
600
800
Time after inclusion (days)
CIBIS II Investigators, Lancet 1999;359:9–13
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)
20
Placebo
15
Mortality
(%)
Metoprolol
10
5
Risk reduction 34%
p=0.0062
0
0
3
6
9
Follow-up (M
12
15
18
21
o n th s)
Hjalmarson A et al. Lancet 1999;353:2001–2007
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – In Whom and When?
Indications:
• Potentially all patients with stable mild and moderate heart failure; patients
with severe heart failure should be referred for specialist advice
• First-line treatment (along with ACE inhibitors) in patients with stable NYHA
class II–III heart failure; start as early as possible
Contra-indications:
• Asthma
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – In Whom and When? (continued)
Cautions/seek specialist advice:
• Severe (NYHA Class IV) heart failure
• Current or recent (<4 weeks) exacerbation of heart failure (e.g. hospital
admission with worsening heart failure)
• Heart block or heart rate <60 beats/min
• Persisting signs of congestion – raised jugular venous pressure, ascites, marked
peripheral oedema
Drug interactions to look out for:
• verapamil/diltiazem (should be discontinued)
• amiodarone
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Where?


In the community in stable patients (NYHA class IV/severe heart failure patients should
be referred for specialist advice)
Not in unstable patients hospitalised with worsening heart failure

Other exceptions – see CAUTIONS/SEEK SPECIALIST ADVICE
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Which and What Dose?



bisoprolol
carvedilol
metoprolol CR/XL
Starting dose
1.25 mg od
3.125 mg bd
12.5–25 mg od
od = once daily; bd = twice daily
Target dose
10 mg od
25–50 mg bd
200 mg od
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – How to Use
•
•
•
•
•
•
•
•
Start with a low dose
Double dose at not less than two-weekly intervals
Aim for target dose or, failing that, the highest tolerated dose
Remember some beta-blocker is better than no beta-blocker
Monitor HR, BP, clinical status (symptoms, signs – especially signs of congestion, and
body weight)
Check blood chemistry 1–2 weeks after initiation and 1–2 weeks after final dose
titration
A specialist heart failure nurse may assist with patient education, follow-up
(in person/by telephone) and dose up-titration
When to down-titrate/stop up-titration – see PROBLEM SOLVING
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Advice to Patient
•
•
•
•
Explain expected benefits (see WHY?)
Emphasise that treatment given as much to prevent worsening of heart failure
as to improve symptoms; beta-blockers also increase survival
If symptomatic improvement occurs, this may develop slowly, 3–6 months or longer
Temporary symptomatic deterioration may occur (estimated 20–30% of cases) during
initiation/up-titration phase
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Advice to Patient (continued)
•
•
Advise patient to report deterioration (see PROBLEM SOLVING) and that deterioration
(tiredness, fatigue, breathlessness) can usually be easily managed
by adjustment
of other medication; patients should be advised not to stop
beta-blocker
therapy without consulting their physician
Patients should be encouraged to weigh themselves daily (after waking, before
dressing, after voiding, before eating) and to increase their diuretic dose should
their
weight increase, persistently (>2 days), by >1.5–2.0 kg
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Problem Solving
Worsening symptoms/signs (e.g. increasing dyspnoea,
fatigue, oedema, weight gain):
• If increasing congestion, double the dose of diuretic and/or halve the dose of betablocker (if increasing diuretic does not work)
• If marked fatigue (and/or bradycardia – see below), halve the dose of beta-blocker
(rarely necessary)
• Review patient in 1–2 weeks; if not improved, seek specialist advice
• If serious deterioration, halve the dose of beta-blocker or stop this treatment (rarely
necessary); seek specialist advice
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Problem Solving (continued)
Low heart rate:
• If <50 beats/min and worsening symptoms – halve the dose of beta-blocker or,
if severe deterioration, stop beta-blocker (rarely necessary)
• Review need for other heart-rate slowing drugs (e.g. digoxin, amiodarone, diltiazem)
• Arrange ECG to exclude heart block
• Seek specialist advice
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— BETA BLOCKERS —
Beta Blockers – Problem Solving (continued)
Asymptomatic low blood pressure:
• Does not usually require any change in therapy
Symptomatic hypotension:
• If dizziness, light-headedness and/or confusion and a low blood pressure occur,
reconsider need for nitrates, calcium channel blockers and other vasodilators
• If no signs/symptoms of congestion, consider reducing diuretic dose
• If these measures do not solve problem, seek specialist advice
NOTE: Beta-blockers should not be stopped suddenly unless absolutely necessary
(there is a risk of a ‘rebound’ increase in myocardial ischaemia/infarction and
arrhythmias); ideally specialist advice should be sought before treatment
discontinuation
Practical recommendations for the use of
ACE inhibitors, beta-blockers and spironolactone in heart failure:
Putting Guidelines into Practice
— SPIRONOLACTONE —
McMurray J, Cohen-Solal A, Dietz R, Eichhorn E, Erhardt L,
Hobbs R, Maggioni A, Pina I, Soler-Soler J, Swedberg K
Eur J Heart Failure 2001;3:495–502
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Format
The practical recommendations for treatment are reviewed under the
following headings:
 Why? – what evidence exists to support the use of these treatments
 In whom and when? – which patients, what contra-indications, what cautions and
drug interactions
 Where? – hospital or primary care setting
 Which agent and what dose? – options offered based on
outcome evidence
 How to use – titration and monitoring information
 Advice to patient – expected benefits and drawbacks
 Problem solving – management of adverse events and concomitant medications
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – Why?
The RALES study showed that low-dose spironolactone increased survival, reduced
hospital admissions and improved NYHA class when added to standard therapy
(diuretic, digoxin, ACE inhibitor and, in a minority of cases, a beta-blocker) in patients
with severe (NYHA class III or IV) heart failure
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
1.00
0.95
Randomized Aldactone Evaluation
Study (RALES)
0.90
0.85
0.80
Probability
of survival
0.75
Spironolactone
0.70
0.65
0.60
0.55
Placebo
0.50
Risk reduction 30%
p<0.001
0.45
0.00
0
3
6
9
12 15 18 21 24 27 30 33 36
Months
Pitt B et al. N Engl J Med 1999;10:709–717
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – In Whom and When?
Indications:
• Potentially all patients with symptomatically moderately severe or severe
heart
failure
• Second-line therapy (after ACE inhibitors and beta-blockers) in patients with
NYHA class III–IV heart failure
Cautions/seek specialist advice:
• Significant renal dysfunction (creatinine >221 µmol/L or 2.5 mg/dL)
• Significant hyperkalaemia (K+ >5.0 mmol/L)
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – In Whom and When? (Continued)
Drug interactions to look out for:
• ACE inhibitors, AT1-receptor blockers, other K+ sparing diuretics (beware
combination preparations, e.g. frusemide plus amiloride or triamterene),
supplements (e.g. KCl)
• NSAIDs
• ‘Low salt’ substitutes with high K+ content
K+
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – Where?
•
•
In the community or in hospital
Exceptions – see CAUTIONS/SEEK SPECIALIST ADVICE
Spironolactone – Which Dose?
•
•
Starting dose: 25 mg od or on alternate days
Target dose: 25–50 mg od
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – How to Use
•
•
•
•
Start at 25 mg once daily
Check blood chemistry at 1, 4, 8 and 12 weeks; 6, 9 and 12 months;
6 monthly thereafter
If K+ rises to between 5.5 and 6.0 mmol/L, or creatinine rises to 2.5 mg/dL
(221 µmol/L), reduce dose to 25 mg on alternate days and monitor blood chemistry
closely
If K+ rises to >6.0 mmol/L, or creatinine to >4.0 mg/dL (354 µmol/L), stop
spironolactone and seek specialist advice
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – Advice to Patient
•
•
•
•
•
Explain expected benefits (see WHY?)
Treatment is given to improve symptoms, prevent worsening of heart failure
and to increase survival
Symptom improvement occurs within a few weeks to a few months of starting
treatment
Avoid NSAIDs not prescribed by a physician (self-purchased ‘over the counter’
treatment, e.g. ibuprofen)
Temporarily stop spironolactone if diarrhoea and/or vomiting occur and contact
physician
Practical Recommendations for Heart Failure Treatment:
Putting Guidelines into Practice
— SPIRONOLACTONE—
Spironolactone – Problem Solving
Worsening renal function/hyperkalaemia:
• See HOW TO USE section
• Major concern is hyperkalaemia (K+ >6.0 mmol/L) though this was uncommon in
RALES; a high-normal K+ may be desirable in heart failure patients, especially if
taking digoxin
• It is important to avoid other K+ retaining drugs (e.g. K+ sparing diuretics) and
nephrotoxic agents (e.g. NSAIDs)
• Some ‘low salt’ substitutes have a high K+ content
• Male patients may develop breast discomfort and/or gynaecomastia